Atria respond to hyperosmotic media with an increase in rate, force, and passive tension dependent on the degree of osmolality and the agent used. Considering the fact that blood osomolality is altered in a number of disease states and treatments, and since the cardiac response to such altered osmolality may be of considerable consequence for patients with incipient or overt cardiovascular disease, we consider it important to further examine the response of cardiac muscle to the hyperosmolar state with particular emphasis on those studies which may shed additional light on the underlying mechanisms involved. Our studies to date have involved the response of spontaneously beating isolated atria. We intend to continue to use this preparation where appropriate as for example in studying the dependence of the hyperosmotic responses on Ca ion level of the bathing media. However, our major effect will be oriented toward intracellular micro-elctrode recording from sinoatrial node cells to determine which aspects of pacemaker electrical activity are altered during the rate response and how this compares with the effect of changes in specific extracellular or intracellular ionic levels. A second major approach will be a more extensive study of the passive tension change associated with hyperosmolality, the degree of its reversibility, and its relation to contracture produced by other agents (caffeine, K ion, Ca ions, etc.). We will utilize the electron microscope to examine ultrastructural changes accompanying the hyperosmolar effect, and in particular those associated with the observed passive tension changes. Finally, additional experiments will be done to determine the force effect independent of the effect on rate, and to examine its interaction with the change in passive tension.